Mechanisms of Disuse Atrophy in Human Skeletal Muscle (iMOB)

University of Nottingham

Status: Active, not recruiting

Conditions: Immobility Syndrome; Muscular Atrophy

Treatments: Behavioral: Single leg immobilisation

Study type: Interventional

Funder types: Other

Identifiers

NCT04199923

1031809

Details and patient eligibility

About

Loss of muscle can be caused by a variety of stimuli and results in reduced mobility and strength and also impacts whole body health. Whilst it is known that muscles waste the process by which this occurs is not well understood. Furthermore, whilst some muscles waste quickly others seem resistant to the effects of disuse.

This study aims to evaluate how quickly changes in muscles start to occur, and investigate the processes which underlie muscle atrophy. By studying muscles which waste quickly and those which are resistant to atrophy this study aims to identify the different processes which lead to muscle loss. This study will also evaluate the differences in muscle changes between young and old people.

Full description

Skeletal muscles host ~40% of all protein in the body. Muscles are not only crucial for locomotion but also represent the body's largest metabolically active tissue, glucose disposal site and fuel reservoir for other organs in pathological conditions (i.e., supply of amino acids to the liver for gluconeogenesis). Muscle atrophy is characterized by a reduction in cross sectional area (CSA) and length and occurs in many common illnesses (e.g. cancers (1), renal/heart failure, sepsis, genetic diseases, neurodegenerative disorders etc). It is also prevalent in situations of reduced neural input such as leg casting after fractures (2), bed-rest, spinal cord injury (3), space flight and chronic physical inactivity. Atrophy results in a loss of muscle power and strength (which is related to increased morbidity and mortality (4)) and reduced capacities for whole-body glucose storage and metabolism which causes insulin resistance. Strategies to oppose atrophy are limited but include mechanical loading (5) and the synergistic anabolic effects of nutrients. Although muscle atrophy is of great clinical importance, relatively little mechanistic research has been done in humans. Thus, the aim of this study is to assess the link between the variation in muscle physiological responses to disuse atrophy with variation in protein turnover and molecular-networks. This will not only provide new hypotheses for physiological regulation of human muscle and generate 'intervention targets' derived from clinically relevant human studies, it will also improve understanding of whether the response to disuse is altered with age and determine if mechanistic differences in atrophy resistant and atrophy sensitive muscles might explain inter-muscular variation in susceptibility to atrophy.

This study aims to define the molecular and metabolic mechanisms causing disuse atrophy in both young and older individuals and explore how and why some muscles are protected against it. The study will also assess temporal aspects of disuse atrophy (in younger individuals only) to explore the mechanistic basis for the more rapid atrophy observed in the early days of disuse.

Enrollment: 36 estimated patients

Sex: Male

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Group 1 and 2: Male, Age 18-40, BMI 18-35
• Group 3: Male, Age 65-80, BMI 18-35

Exclusion criteria

• BMI > 35 / <18
• Female
• Personal or Family History of Venous Thromboembolism
• Significant medical comorbidities

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

15 Day immobilisation

Experimental group

Description:

The dominant leg of young healthy patients (18-40 years without serious comorbidities) will be immobilised using a fixed knee brace and aircast boot for 15 continuous days

Treatment:

Behavioral: Single leg immobilisation

5 Day immobilisation young

Experimental group

Description:

The dominant leg of young healthy patients (18-40 years without serious comorbidities) will be immobilised using a fixed knee brace and aircast boot for 5 continuous days

Treatment:

Behavioral: Single leg immobilisation

5 Day immobilisation old

Experimental group

Description:

The dominant leg of aged patients (65-80 years without serious comorbidities) will be immobilised using a fixed knee brace and aircast boot for 5 continuous days

Treatment:

Behavioral: Single leg immobilisation